Type II disbetes mellitus is a metabolic disturbance disease, and the patients exhibit mainly the symptoms of increased blood sugar concentration (the fasting blood sugar concentration is over 130 mg/dL) and glycosuria. Long-term hyperglycemia may cause the occurrence of various complicating diseases, such as pathological changes in the retina, the kidney and the nervous system. Among others, the cardiovascular complicating diseases are the main cause of the diabetic patients being dead or disabled [Shinkai, H. Exp. Opin. Ther. Patents. 2000, 10: 596]. Therefore, it is very important to control the patients' blood sugar concentration for inhibiting or blocking the occurrence of the complicating diseases. Currently, the sulfonylurea drugs for stimulating the scretion of insulin and the biguanide drugs are used clinically to control the patients' blood sugar concentration. Since the insulin resistance is the main pathogenesis of the type II diabetes mellitus, the insulin-sensitizing agent is an important trend in the research of drugs against the type II diabetes mellitus. The first thiozolidinedione insulin-sensitizer, troglitazone, is presented on the market in 1997. This drug as well as other drugs of the same kind available on the market later, pioglitazone and rosiglitazone, can control clinically the patients' blood sugar concentration well. However, the thiozolidinedione drugs exhibit the hepatotoxicity of different extents [Henry, R. R. Endocrinol. Metab. Clin. North Am. 1997, 26, 553]. And the troglitazone is withdrawn from the market due to its serious hepatotoxicity. The toxicity of this type of compounds was suspected to be related to the thiazolidinedione group. So the study of insulin-sensitizers has shifted to the synthesis and development of non-thiazolidinedione compounds for anti-type II diabetes treatment.
One object of the present invention is to provide the novel benzopyran compounds with the insulin-sensitizing activities and the pharmaceutical acceptable salts thereof.
Another object of the present invention is to provide the preparative methods for the benzyopyran compounds and their salts.
A further object of the present invention is to provide the application of the benzopyran compounds and their salts in the preparation of the drugs against type II diabetes mellitus.
Methods of treating type II disbetes with the compounds of the present invention are also described herein.